7e21

Cryo EM structure of a Na+-bound Na+,K+-ATPase in the E1 state with ATP-gamma-SCryo EM structure of a Na+-bound Na+,K+-ATPase in the E1 state with ATP-gamma-S

Structural highlights

7e21 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.9Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

AT1A1_HUMAN Autosomal dominant Charcot-Marie-Tooth disease type 2DD;Primary hypomagnesemia-refractory seizures-intellectual disability syndrome. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

AT1A1_HUMAN This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients (PubMed:29499166, PubMed:30388404). Could also be part of an osmosensory signaling pathway that senses body-fluid sodium levels and controls salt intake behavior as well as voluntary water intake to regulate sodium homeostasis (By similarity).[UniProtKB:Q8VDN2]^[1] ^[2]

Publication Abstract from PubMed

Sodium-Potassium Pump (Na(+)/K(+)-ATPase, NKA) is an ion pump that generates an electrochemical gradient of sodium and potassium ions across the plasma membrane by hydrolyzing ATP. During each Post-Albers cycle, NKA exchanges three cytoplasmic sodium ions for two extracellular potassium ions through alternating changes between the E1 and E2 states. Hitherto, several steps remained unknown during the complete working cycle of NKA. Here, we report cryo-electron microscopy (cryo-EM) structures of recombinant human NKA (hNKA) in three distinct states at 2.7-3.2 A resolution, representing the E1.3Na and E1.3Na.ATP states with cytosolic gates open and the basic E2.[2K] state, respectively. This work provides the insights into the cytoplasmic Na(+) entrance pathway and the mechanism of cytoplasmic gate closure coupled with ATP hydrolysis, filling crucial gaps in the structural elucidation of the Post-Albers cycle of NKA.

Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states.,Guo Y, Zhang Y, Yan R, Huang B, Ye F, Wu L, Chi X, Shi Y, Zhou Q Nat Commun. 2022 Jul 8;13(1):3957. doi: 10.1038/s41467-022-31602-y. PMID:35803952^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lassuthova P, Rebelo AP, Ravenscroft G, Lamont PJ, Davis MR, Manganelli F, Feely SM, Bacon C, Brozkova DS, Haberlova J, Mazanec R, Tao F, Saghira C, Abreu L, Courel S, Powell E, Buglo E, Bis DM, Baxter MF, Ong RW, Marns L, Lee YC, Bai Y, Isom DG, Barro-Soria R, Chung KW, Scherer SS, Larsson HP, Laing NG, Choi BO, Seeman P, Shy ME, Santoro L, Zuchner S. Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Am J Hum Genet. 2018 Mar 1;102(3):505-514. doi: 10.1016/j.ajhg.2018.01.023. PMID:29499166 doi:http://dx.doi.org/10.1016/j.ajhg.2018.01.023
↑ Schlingmann KP, Bandulik S, Mammen C, Tarailo-Graovac M, Holm R, Baumann M, Konig J, Lee JJY, Drogemoller B, Imminger K, Beck BB, Altmuller J, Thiele H, Waldegger S, Van't Hoff W, Kleta R, Warth R, van Karnebeek CDM, Vilsen B, Bockenhauer D, Konrad M. Germline De Novo Mutations in ATP1A1 Cause Renal Hypomagnesemia, Refractory Seizures, and Intellectual Disability. Am J Hum Genet. 2018 Nov 1;103(5):808-816. doi: 10.1016/j.ajhg.2018.10.004. PMID:30388404 doi:http://dx.doi.org/10.1016/j.ajhg.2018.10.004
↑ Guo Y, Zhang Y, Yan R, Huang B, Ye F, Wu L, Chi X, Shi Y, Zhou Q. Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states. Nat Commun. 2022 Jul 8;13(1):3957. PMID:35803952 doi:10.1038/s41467-022-31602-y

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OCA

[1] Lassuthova P, Rebelo AP, Ravenscroft G, Lamont PJ, Davis MR, Manganelli F, Feely SM, Bacon C, Brozkova DS, Haberlova J, Mazanec R, Tao F, Saghira C, Abreu L, Courel S, Powell E, Buglo E, Bis DM, Baxter MF, Ong RW, Marns L, Lee YC, Bai Y, Isom DG, Barro-Soria R, Chung KW, Scherer SS, Larsson HP, Laing NG, Choi BO, Seeman P, Shy ME, Santoro L, Zuchner S. Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2. Am J Hum Genet. 2018 Mar 1;102(3):505-514. doi: 10.1016/j.ajhg.2018.01.023. PMID:29499166 doi:http://dx.doi.org/10.1016/j.ajhg.2018.01.023

[2] Schlingmann KP, Bandulik S, Mammen C, Tarailo-Graovac M, Holm R, Baumann M, Konig J, Lee JJY, Drogemoller B, Imminger K, Beck BB, Altmuller J, Thiele H, Waldegger S, Van't Hoff W, Kleta R, Warth R, van Karnebeek CDM, Vilsen B, Bockenhauer D, Konrad M. Germline De Novo Mutations in ATP1A1 Cause Renal Hypomagnesemia, Refractory Seizures, and Intellectual Disability. Am J Hum Genet. 2018 Nov 1;103(5):808-816. doi: 10.1016/j.ajhg.2018.10.004. PMID:30388404 doi:http://dx.doi.org/10.1016/j.ajhg.2018.10.004

[3] Guo Y, Zhang Y, Yan R, Huang B, Ye F, Wu L, Chi X, Shi Y, Zhou Q. Cryo-EM structures of recombinant human sodium-potassium pump determined in three different states. Nat Commun. 2022 Jul 8;13(1):3957. PMID:35803952 doi:10.1038/s41467-022-31602-y

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